AB0383 COMPARISON OF EFFICACY AND SAFETY IN JAK INHIBITOR DUE TO A DIFFERENCE OF SELECTIVITY – TOFACITINIB vs. BARICITINIB –
Authors: I. Yoshii, N. Sawada, T. Chijiwa
Journal: Annals of the Rheumatic Diseases (2022)

Background Each Janus Kinase Inhibitor (JAK-i) has different selectivity of JAKs, such as JAK1, JAK2, JAK3, and TIK2. However, little has been known regarding mode of action due to the selectivity difference in clinical practice for treating rheumatoid arthritis (RA). Objectives The aim of this study is to compare difference of efficacy and safety in two JAK-i; between tofacitinib (TOF) and baricitinib (BAR) in clinical practice using one-center retrospective cohort. Methods Within the case which administered TOF or BAR to the RA patient who the effect was insufficient in the existing treatment and the disease activity was over the middle disease activity using simplified disease activity index (SDAI). At the start of administration (baseline), 5 mg tablets of TOF were taken twice a day or 4 mg tablets of BAR were taken one a day. Patients were divided by drug and included their sex, age at onset, anti-cyclic citrullinated polypeptide antibodies (ACPA) titer, length of RA history at onset, Sharp/van der Heijde score (SHS) at onset, Naïve/Not Naive for biologic DMARDs or JAK-i, 28-joints disease activity score (DAS28), SDAI, Health Assessment Questionnaire Disability Index (HAQ-DI), and pain score with visual analog scale (PS-VAS). It was classified into large joint and small joint, and the point was independently scored by swelling and pressure pain by size and position in each joint. Total score of the involved joints for each part; upper-extremities, lower extremities, big joints, and small joints (UES/LES/BJS/SJS), rheumatoid factor (RF) titer, serum matrix metalloprotease-3 (MMP-3) level, serum creatinine (Cr) level, and estimated glomerular filtration rate (eGFR) of each part were measured. The mean values of each group were obtained at baseline, 1, 2, 3, 6, 9, and 12 months, and the two groups were statistically compared using the Mann-Whitney U-test. As a sub-analysis, each drug group was divided into bio or JAK-i naive, age ≥ 70 years, disease duration ≥ 10 years, SHS ≥ 100. The change of DAS28 under each 2 divided condition was compared using Mann-Whitney U-test. Similar comparison was carried out with RA patient who administered golimumab (GOL) as a control group. The significance level was less than 5%. Continuation rate (the withdrawal after the remission introduction is put in the continuation) in 12 months after baseline was also compared. Results A total of 82 patients were picked up, in whom 22 TOF group, 31 BAR group, and 29 GOL group included. Both DAS28 and SDAI were consistently lower in the BAR than in the other 2 groups from 1 month after baseline. SDAI in the BAR was significantly lower than in the GOL at 3 months after the baseline. The HAQ-DI score at 6 months after baseline was significantly lower in the BAR than in the GOL. PS-VAS in the GOL was significantly higher than the other two groups at 2, 3 and 6 months after baseline. In the joint point, BJS in the BAR was significantly lower than that in the GOL at 2, 3, and 6 month after baseline. SJS in the GOL was significantly lower than that in the TOF at 6 and 12 months after baseline. There was no significant difference in MMP -3, RF, Cr and eGFR between the 3 groups in any observation month, but Cr increased after the start in the BAR group and eGFR tended to decrease. In the sub-analysis, the decrease of DAS28 at 1 year after baseline with a history of ≥ 10 years was significantly greater than in those with a history of &lt; 10 years in the TOF, as well as DAS28 at 1 year in those with SHS ≥ 100 decreased significantly more than that in those &lt; 100. These phenomena was not observed in the BAR group. The continuation rate at 12 months after the start of administration was 86.4% in the TOF, 89.3% in the BAR and 69.0% in the GOL. Conclusion Even JAK-i characteristics in action differs for each drug. It is needed to choose appropriate drug based on these drug characteristics. Disclosure of Interests None declared